Precooled cryogenic ablation system

ABSTRACT

A method and apparatus for using a secondary refrigerant to precool and liquefy a primary refrigerant, then vaporizing and expanding the primary refrigerant to cool a cold tip of a cryosurgical instrument for ablation of biological tissue, such as cardiovascular tissue, in particular endocardiac tissue and tissue inside a cardiac blood vessel. The secondary refrigerant has a critical temperature above the critical temperature of the primary refrigerant, and a cooling temperature below the critical temperature of the primary refrigerant, thereby facilitating the use of the precooling step to provide liquid primary refrigerant in an operating room environment in which the primary refrigerant could not otherwise be provided in the liquid phase.

Notice: More than one reissue application has been filed for the reissueof U.S. Pat. No. 6,237,355. The reissue applications are applicationSer. Nos. 11/412,250 (the present application) and 10/446,390 (which isfully incorporated herein by reference). The present application Ser.No. 11/412,250, is a divisional of reissue application Ser. No.10/446,390 and also a reissue of U.S. Pat. No. 6,237,355.

CROSS REFERENCE TO RELATED APPLICATIONS

Not Applicable

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention is in the field of cooling biological tissues to very lowtemperatures, for treatment of medical conditions, as in cryosurgery.

2. Background Information

It is desirable to be able to selectively cool miniature discreteportions of biological tissue to very low temperatures in theperformance of cryosurgery, without substantially cooling adjacenttissues of the organ. Cryosurgery has become an important procedure inmedical, dental, and veterinary fields. Particular success has beenexperienced in the specialties of gynecology and dermatology. Otherspecialties, such as neurosurgery and urology, could also benefit fromthe implementation of cryosurgical techniques, but this has onlyoccurred in a limited way. Unfortunately, currently known cryosurgicalinstruments have several limitations which make their use difficult orimpossible in some such fields. Specifically, known systems can notachieve the necessary temperature and cooling power to optimally performcryosurgical ablation, such as in cardiac ablation to correctarrhythmia.

In the performance of cryosurgery, it is typical to use a cryosurgicalapplication system designed to suitably freeze the target tissue,thereby destroying diseased or degenerated cells in the tissue. Theabnormal cells to be destroyed are often surrounded by healthy tissuewhich must be left uninjured. The particular probe, catheter, or otherapplicator used in a given application is therefore designed with theoptimum shape, size, and flexibility or rigidity for the application, toachieve this selective freezing of tissue. Where a probe or catheter isused, the remainder of the refrigeration system must be designed toprovide adequate cooling, which involves lowering the operative portionof the probe to a desired temperature, and having sufficient power orcapacity to maintain the desired temperature for a given heat load. Theentire system must be designed to place the operative portion of theprobe or catheter at the location of the tissue to be frozen, withouthaving any undesirable effect on other organs or systems.

It is an object of the present invention to provide a method andapparatus for precooling a primary loop high pressure refrigerant to apoint below its critical temperature, to liquefy the primaryrefrigerant, with a secondary loop refrigeration cycle. This allows theuse of a liquid primary refrigerant having a critical temperature belowthe operating room temperature, in order to achieve the lowertemperature possible with such a primary refrigerant.

BRIEF SUMMARY OF THE INVENTION

The present invention comprises a miniature refrigeration system,including a method for operating the system, including precooling of theprimary high pressure refrigerant below its critical temperature, toliquefy the primary refrigerant, with a secondary refrigeration cycleusing a second refrigerant with a higher critical temperature, tomaximize the available cooling power of the primary refrigerant, and toachieve the lowest possible temperature.

The cooling power is an important design parameter of a cryosurgicalinstrument. With greater cooling power, more rapid temperature decreasesoccur, and lower temperatures can be maintained at the probe tip duringfreezing. This ultimately leads to greater tissue destruction. The powerof a J-T cryosurgical device is a function of the enthalpy difference ofthe primary refrigerant and the mass flow rate. Pre-cooling arefrigerant below its critical temperature and liquefying therefrigerant will increase the enthalpy difference available for coolingpower.

An example of a suitable primary refrigerant is SUVA-95, a mixture ofR-23 and R-116 refrigerants made by DuPont Fluoroproducts, ofWilmington, Del. SUVA-95 has a critical temperature of 287K, withcooling capacity at temperatures as low as 185K at one atmosphere. Anexample of a suitable secondary refrigerant is AZ-20, an R-410arefrigerant made by Allied Signal of Morristown, N.J. AZ-20 has acritical temperature of 345K, with cooling capacity at temperatures aslow as 220K at one atmosphere.

The high pressure primary refrigerant is fed as a gas into a highpressure passageway within a primary-to-secondary heat exchanger. Theprimary-to-secondary heat exchanger can be a coiled tube heat exchangeror a finned tube heat exchanger. The liquid secondary refrigerant isvaporized and expanded into a low pressure passageway in theprimary-to-secondary heat exchanger. Heat exchange between the lowpressure secondary refrigerant vapor and the high pressure primaryrefrigerant cools and liquefies the high pressure refrigerant. Theliquid high pressure primary refrigerant is then vaporized and expandedat the cooling tip of a cryosurgical catheter to provide the coolingpower necessary for effective ablation of tissue. The method andapparatus of the present invention can be used equally well in a rigidhand held cryoprobe, or in a catheter.

The primary-to-secondary heat exchanger is part of the secondaryrefrigeration system, which can have a secondary compressor and asecondary expansion element, in addition to the primary-to-secondaryheat exchanger. The liquid high pressure secondary refrigerant, having ahigher critical temperature than the primary refrigerant, can be at atemperature which is relatively higher than the critical temperature ofthe primary refrigerant. However, the vaporized and expanded lowpressure secondary refrigerant is at a temperature which is low enoughto cool the primary refrigerant below its critical temperature. Sincethe secondary refrigerant has a critical temperature above normaloperating room temperature, it can easily be provided in the liquidstate in an operating room environment, whereas the primary refrigerant,which has a critical temperature significantly below normal operatingroom temperature, can not.

The liquid high pressure primary refrigerant is conducted from the heatexchanger to the inlet of a primary Joule-Thomson expansion elementlocated in the cold tip of the probe or catheter, where the primaryrefrigerant is vaporized and expanded to a lower pressure and a lowertemperature.

The primary refrigerant exiting the primary Joule-Thomson expansionelement is exposed to the inner surface of a heat transfer element atthe cold tip. The vaporized and expanded primary refrigerant cools theheat transfer element to a lower temperature and then returns throughthe low pressure return passageway of the catheter or probe.

The novel features of this invention, as well as the invention itself,will be best understood from the attached drawings, taken along with thefollowing description, in which similar reference characters refer tosimilar parts, and in which:

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a schematic view of the preferred embodiment of the apparatusof the present invention; and

FIG. 2 is a schematic section view of the primary-to-secondary heatexchanger used in the apparatus shown in FIG. 1.

DETAILED DESCRIPTION OF THE INVENTION

The present invention lies in the appropriate use of a secondaryevaporative refrigeration system to precool and liquefy the primary highpressure refrigerant, before passage of the primary refrigerant througha primary Joule-Thomson expansion element. This is intended to enablethe generation of a sufficiently low temperature, and to maximize theavailable cooling power, at the cold tip of a cryosurgical probe orcatheter.

Pre-cooling the primary refrigerant to an at least partially liquidstate, prior to feeding it to the primary expansion element, is thefocus of the present invention. This pre-cooling can be done prior tointroducing the primary refrigerant into the catheter, by the use of aheat exchanger in a cooling console. Alternatively, pre-cooling can beprovided nearer to the treatment area, such as in the handle of acryoprobe, or at the proximal end of a catheter.

An important parameter in the design of a cryosurgical device is thecooling power which the refrigeration system can develop. The coolingpower determines the rate of cooling in degrees per accord, and thetemperature which can be maintained at the probe tip during freezing ofthe tissue. The rate of freezing is important in achieving cell death,since more rapid freezing results in better formation of intracellularice crystals, resulting in cell lysis. The rate of freezing alsodetermines the length of time required to perform a given procedure onthe patient. The quicker the procedure, the less traumatic the procedureis to the patient.

The temperature which can be maintained at the probe cold tip determinesthe size of the ice ball formed in the surrounding tissue. This, ofcourse, determines the total volume of tissue destroyed at eachlocation, and the speed with which the procedure can be completed.

In Joule-Thomson cryosurgical devices, high pressure fluid expandsacross a restriction of some kind, such as a small orifice, or arestricted tube. The sudden drop in pressure results in a correspondingdrop in temperature. The cooling power of the device is the product ofthe mass flow rate of the cryogen and the enthalpy difference at thedifferent pressures and temperatures. The flow rate is a function oforifice size and the temperature and pressure of the cryogen. For agiven orifice size, under non-choking conditions, the density of thecryogen is higher at higher pressures and lower temperatures, resultingin a higher mass flow rate. The maximum flow rate is found at the pointwhere the cryogen is a liquid. The enthalpy difference is also afunction of the pressure and temperature. For a given temperature and agiven pressure, the maximum enthalpy difference between two conditionsoccurs at the liquefaction point of the cryogen. Incorporating apre-cooling heat exchanger into the refrigeration system, to promoteliquefaction of the high pressure primary cryogen, increases the powerof the system.

If the primary refrigerant is in the gaseous state upon startup of therefrigeration system, the early flow rate is very low, and the power isvery low. Therefore, the initial cool down is very slow at overcomingthe low flow rate. Further, the cold tip is typically placed within thepatient, and in contact with the target tissue, before commencement ofcooldown, placing a significant heat load on the tip. This means thatcooldown can be unacceptably slow, and in some cases, it may not occurat all.

In order to maximize the performance of the present cryosurgical system,and to eliminate the problems normally associated with slow cooldownrates and low cooling power, an independent secondary evaporativerefrigeration system is incorporated. The primary system uses arefrigerant such as freon, or SUVA-95, to achieve the desiredtemperature and capacity at the cold tip. However, the criticaltemperature of such a refrigerant is below the temperature normallyfound in the operating room environment, so provision of the primaryrefrigerant in the liquid state requires precooling. The secondarysystem uses a refrigerant such as AZ-20, to pre-cool and liquefy theprimary refrigerant prior to flow of the primary refrigerant to the coldtip. The secondary system accomplishes this pre-cooling through aprimary-to-secondary heat exchanger. This pre-cooling causes the initialflow rate and the cooling power of the system to be higher, making theinitial cooldown rate much faster.

As shown in FIG. 1, the apparatus 10 of the present invention includes asource of gaseous high pressure primary refrigerant 12, a source ofliquid high pressure secondary refrigerant 14, a primary-to-secondaryheat exchange unit 16, and a probe or catheter 18 with a cold tip 20.The gaseous primary refrigerant source 12 can incorporate a pressurebottle as schematically shown, with the primary loop being an open loop,or the source 12 can incorporate a compressor, with the primary loopbeing a closed loop, as will be explained below. The primary refrigerantis one which, in order to deliver the desired temperature and coolingcapacity at the cold tip 20, necessarily has a critical temperaturebelow the temperature of the operating room environment. The purpose ofthe present invention is to cool that gaseous primary refrigerant belowits critical temperature and convert it to a liquid refrigerant, inorder to achieve the desired temperature and cooling capacity. Aflexible coaxial catheter 18 can be constructed with an outer tube madeof pebax, and an inner tube made of polyimide.

Gaseous high pressure primary refrigerant flows from the primaryrefrigerant source 12 via a conduit 32 into the heat exchange unit 16.After heat exchange and liquefaction, liquid primary refrigerant, at atemperature below the temperature of the operating room environment,flows from the heat exchange unit 16 into the catheter or probe 18. Nearthe distal tip of the catheter 18, the liquid primary refrigerant isvaporized and expanded at an expansion element shown schematically as anorifice 36. This lowers the temperature of the primary refrigerant tothe desired temperature, enabling the refrigerant to cool the cold tip20 to the selected temperature for tissue ablation. Gaseous primaryrefrigerant returning from the cold tip 20 exits the heat exchange unit16 via a conduit 34. Where the primary refrigerant source 12incorporates a pressure bottle, the primary loop can be operated as anopen loop, and the gaseous primary refrigerant conduit 34 can becollected by a compressor 22 to vent to atmosphere or to a collector 24.Alternatively, the primary loop can be operated as a closed loop, andthe gaseous primary refrigerant conduit 32 can be routed (not shown)from the outlet of the compressor 22, as is well know in the art.

The liquid secondary refrigerant source 14 can incorporate a compressorunit as schematically shown, or it can incorporate a pressure bottle. Ifrequired to generate the necessary pressure for liquefaction of thesecondary refrigerant, a compressor can be used to raise the pressure ofthe effluent from a pressure bottle. The secondary refrigerant source 14can also include a condenser, as is well known in the art, forliquefying the secondary refrigerant, if required. The secondaryrefrigerant must be one which has a critical temperature above thetemperature of the operating room environment, so that the secondaryrefrigerant can be conducted in liquid form to the primary-to-secondaryheat exchange unit 16. This enables the use of the phase-change enthalpydifference in the secondary refrigerant to provide the necessary coolingto take the primary refrigerant below its critical temperature to theheat exchange unit 16.

Liquid high pressure secondary refrigerant, at a temperature above thetemperature of the operating room environment, flows from the secondaryrefrigerant source 14 via a conduit 28 into the heat exchange unit 16.After vaporization and heat exchange, gaseous secondary refrigerantflows from the heat exchange unit 16 via a conduit 30. Where thesecondary refrigerant source 14 incorporates a pressure bottle, thesecondary loop can be operated as an open loop, and the gaseoussecondary refrigerant conduit 30 can vent to atmosphere or in acollector (not shown) as is well known in the art. Alternatively, thesecondary loop can be operated as a closed loop, and the gaseoussecondary refrigerant conduit 30 can be routed to the inlet of acompressor in the secondary refrigerant source 14, as shown.

As shown schematically in FIG. 2, liquid high pressure secondaryrefrigerant enters the heat exchange unit 16 via a supply conduit 28 andis vaporized and expanded via a secondary expansion element shown as acapillary tube 29. The vaporized and expanded secondary refrigerant, ata temperature below the critical temperature of the primary refrigerant,then flows through a secondary refrigerant flow path in aprimary-to-secondary heat exchanger 26 and exits the heat exchange unit16 via a return conduit 30.

Gaseous high pressure primary refrigerant enters the heat exchange unit16 via a supply conduit 32 and flows through a primary refrigerant flowpath in the heat exchanger 26. Since the temperature of the secondaryrefrigerant flowing through the heat exchanger 26 is significantly belowthe critical temperature of the primary refrigerant, the primaryrefrigerant is liquefied in the heat exchanger 26. Liquid primaryrefrigerant then exits the heat exchanger via a conduit 33 and flowsthrough the catheter 18 to a primary expansion element, shownschematically as an orifice 36, near the cold tip 20. The primaryexpansion element 36 vaporizes and expands the primary refrigerant tothe selected temperature for cooling the cold tip 20 to the desiredtemperature for ablation of tissue. The vaporized and expanded primaryrefrigerant returning from the cold tip 20 then flows back through thecatheter 18, through the heat exchange unit 16, and exits the heatexchange unit 16 via a return conduit 34.

While the particular invention as herein shown and disclosed in detailis fully capable of obtaining the objects and providing the advantageshereinbefore stated, it is to be understood that this disclosure ismerely illustrative of the presently preferred embodiments of theinvention and that no limitations are intended other than as describedin the appended claims.

1. A cryosurgical instrument for ablation of endocardiac tissue,comprising: a source of a gaseous primary refrigerant said sourceproviding said primary refrigerant at a temperature above the criticaltemperature of said primary refrigerant; a source of a liquid secondaryrefrigerant, said secondary refrigerant having a critical temperaturehigher than said critical temperature of said primary refrigerant; asecondary expansion element connected to receive said liquid secondaryrefrigerant, said secondary expansion element being constructed tovaporize and expand said secondary refrigerant to a temperature belowsaid critical temperature of said primary refrigerant; aprimary-to-secondary heat exchanger having a primary refrigerant flowpath connected to receive said gaseous primary refrigerant, and asecondary refrigerant flow path connected to receive said vaporized andexpanded secondary refrigerant from said secondary expansion element,said heat exchanger being constructed to cool and liquefy said primaryrefrigerant; a primary expansion element connected to receive saidliquid primary refrigerant from said heat exchanger, said primaryexpansion element being constructed to vaporize and expand said primaryrefrigerant to a selected cryogenic temperature; and a cryoablation heattransfer element connected to receive said vaporized and expandedprimary refrigerant; wherein said primary refrigerant comprises SUVA-95,and said secondary refrigerant comprises AZ-20.
 2. A cryosurgicalinstrument for ablation of cardiac tissue, comprising: a source of agaseous primary refrigerant, wherein said primary refrigerant is asingle gas and has a critical temperature; a source of a liquidsecondary refrigerant, said secondary refrigerant having a criticaltemperature higher than said critical temperature of said primaryrefrigerant; a secondary expansion element connected to receive saidliquid second refrigerant, said secondary expansion element beingconstructed to vaporize and expand said secondary refrigerant to atemperature below said critical temperature of said primary refrigerant;a primary-to-secondary heat exchanger having a primary refrigerant flowpath connected to receive said gaseous primary refrigerant, and asecondary refrigerant flow path connected to receive said vaporized andexpanded secondary refrigerant from said secondary expansion element,said heat exchanger being constructed to cool and liquefy said primaryrefrigerant; a primary expansion element connected to receive saidliquid primary refrigerant from said heat exchanger, said primaryexpansion element being constructed to vaporize and expand said primaryrefrigerant to a selected cryogenic temperature; and a cryoablation heattransfer element connected to receive said vaporized and expandedprimary refrigerant.
 3. A cryosurgical instrument as recited in claim 2further comprising: a first conduit connecting said primary-to-secondaryheat exchanger in fluid communication with said primary expansionelement for flowing said liquid primary refrigerant from said heatexchanger to said primary expansion element; and a second conduitjuxtaposed with said first conduit for back flowing said primaryrefrigerant from said primary expansion element for exit through saidprimary-to-secondary heat exchanger.